Angelica sinensis is a Chinese medicinal herb for treating gynecological and gastrointestinal disorders, and also in conjunction with cancer chemotherapy. Aim of the study: In the present study, the cytotoxic and anti-proliferative effects of three main Angelica sinensis phthalicles, namely n-butylidenephthalide (BLP), senkyunolide A (SKA) and z-ligustilide (LGT), and their synergy on colon cancer HT-29 cells were investigated. Moreover, the results obtained in both human colon cancer HT-29 and normal colon CCD-18Co cells were compared for the investigation of selectivity. Materials and methods: MTT and [H-3] thymidine incorporation assays were used for the evaluation of cytotoxic and anti-proliferative effects, respectively. Interactions among phthalicles were determined by median-effect analysis. Results: All three phthalides dose-dependently decreased cell viability more potently in HT-29 than in CCD-18Co cells. The IC50 values for inhibition of cell proliferation for SKA, LGT and BLP were 54.17 +/- 5.10, 60.63 +/- 6.79 and 236.90 +/- 18.22 mu M, respectively, in HT-29 cells. Angelica sinensis extract demonstrated significant synergy in inhibiting cell proliferation. Conclusions: The three phthalicles might have anti-cancer potential, yet the phthalicles, in combination with other ingredients in Angelica sinensis extract, display significant synergy leading to a stronger antitumor effect. (C) 2008 Elsevier Ireland Ltd. All rights reserved.